It is now clear that cavitation-related phenomena are responsible for a variety of side-effects of lithotripter procedures and play an important role in the fragmentation of the stones as well. Systematic studies have shown that the thresholds for tissue damage are as much as an order of magnitude lower than the shock pressures needed to break stones. Because the behavior of bubbles in the confined environment of the body is different than in infinite fluids, classical cavitation studies provide only a qualitative guide to the processes which take place in tissues. Specifically, it is hypothesized that negative pressures are less important and thresholds are higher for bubbles in tissues than in fluids. A thorough investigation of the role of cavitation in lithotripsy not only will shed light on the mechanisms by which intense shock waves act on stones and the tissues of the body but this qualitatively new perspective will also add to knowledge of the action of intense pulsed ultrasonic waves which are used in diagnosis. The proposed program has three broad closely interrelated phases. One is concerned with the effects of these fields on the soft tissues of the body (the side effects of lithotripsy). The second concerns the mechanisms of stone fragmentation (lithotripsy). The third provides the physical basis for the generation, propagation and detection of the acoustic fields and the analytical basis for the interaction of the waves with bubbles, tissues and stones. The work requires not only a new theoretical approach to bubble behavior in tissues, but, for experimental studies to have relevance to lithotripsy, they must concentrate on mammalian tissues. To test these hypotheses, experiments will proceed systematically to determine threshold pressure amplitudes, the relative importance of compressional and rarefactional pressures, the importance of pulse number, shock characteristics of the wave and the frequency composition of the exposure fields. The physiological endpoints of the experimental studies will include structural and functional changes in kidney, liver, lung and heart and developmental effects in the embryo/fetus. The ideal treatment would maximize stone fragmentation while minimizing tissue damage. To study fragmentation, fundamental mechanical properties of human stones including mechanical hardness, fracture toughness, flaw size distribution, energy of breaking, gas content and strain-rate-dependent fracture characteristics will be determined. Numerical and experimental studies will be used to determine stresses within stones, to predict the thresholds for cavitation in and near stones and to relate these data to observed fracture phenomena. Clinically oriented studies will categorize stone types with regard to their ease of fracture, identify protocols that can induce surface cracks in stones that aid fragmentation and identify coupling liquid properties that increase the efficiency of stone destruction. Newly developed analytical and experimental tools will be used in the design of shock wave sources and in the prediction and measurement of lithotripter fields in tissues.